Primary cilia and BBS4 are required for postnatal pituitary development

Abstract

Primary cilia orchestrate several signaling pathways, and their disruption results in pleiotropic disorders called ciliopathies. Bardet Beidl syndrome (BBS), one such ciliopathy, provides insights into cilia function in many tissues. Using a mouse model of BBS, Bbs4 knockout (Bbs4-/-), and conditional deletion of pituitary cilia, we found that adult Bbs4-/- and cilia-less pituitaries are hypoplastic and have increased gonadotroph populations. The developing Bbs4-/- pituitary experiences mildly reduced Hedgehog signaling. Isolated Bbs4-/- pituitary stem cells exhibited reduced Hedgehog signal responsiveness and expression of stem cell markers. These data demonstrate that cilia and BBS function are necessary for pituitary growth. We propose that altered pituitary cilia-mediated patterning contribute to physiological features of ciliopathies such as BBS. Summary statementA mouse model of BBS reveals that ciliary Hedgehog signaling is necessary for postnatal pituitary development.